We have studied and sequenced a thyroid hormone-regulated rat liver mRNA (4-12B) and showed that it is related to the superfamily of serine protease inhibitors, with the highest similarity to mouse contrapsin. The optimized alignment with the related sequences indicates that lysine-serine residues are located at the reactive site or adjacent to it. This suggests that 4-12B mRNA could code for the protein contributing to the serum trypsin inhibiting activity in rat. These protease inhibitors control proteolytic degradation responsible for immune reactions, coagulation and inflammation. This finding, that a protease inhibitor is transcriptionally regulated by T3, could represent a previously unrecognized mechanism by which thyroid hormone might affect any of several important physiological processes. Regulation of malic enzyme mRNA by a high carbohydrate diet is liver specific. Furthermore, the amplitude of the response depends on the thyroidal state of the animal, being lower by a factor of about 4 in hypothyroidism and higher in hyperthyroidism. Mathematical modeling shows that this increase in cytoplasmic mRNA is compatible with retarded degradation of cytoplasmic mRNA while thyroid hormone regulates the synthesis of this mRNA predominantly at the nuclear level.